Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione
Liang J, Jahraus B, Balta E, Ziegler JD, Hübner K, Blank N, Niesler B, Wabnitz GH, Samstag Y
Frontiers in immunology · 59 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- Deutsche Forschungsgemeinschaft
- Grants
- Deutsche Forschungsgemeinschaft (SA 393/3-4)
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-11-14 · Front Immunol · vol. 9 · p. 2584
- Publisher
- Frontiers Media
- Cited
- 77 citations · more than 94% of similar papers · 3.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 63 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · IL-33, ST2, and ILC Pathways · Psoriasis: Treatment and Pathogenesis
- Keywords
- Sulforaphane, Glutathione, Oxidative stress, Reactive oxygen species, Chemistry, Inflammation, RAR-related orphan receptor gamma, Transcription factor, T cell, Immune system, Antioxidant, Cell biology, Immunology, Pharmacology, Biochemistry, Biology, Enzyme
- MeSH
- t-lymphocytes, cells, cultured, humans, brassicaceae, arthritis, rheumatoid, inflammation, reactive oxygen species, isothiocyanates, sulfoxides, glutathione, anti-inflammatory agents, interleukins, interleukin-17, down-regulation, stat3 transcription factor, nuclear receptor subfamily 1, group f, member 3, primary cell culture, immunosuppression therapy, interleukin-22
9 authors
From DE
- Jie LiangHeidelberg University
- Beate JahrausHeidelberg University
- Emre BaltaHeidelberg University
- Jacqueline D. ZieglerHeidelberg University
- Katrin HübnerHeidelberg University
- Norbert BlankHeidelberg University
Abstract
The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for inflammation, e.g., in rheumatoid arthritis. Therefore, balancing the T-cell redox milieu may represent a promising new option for therapeutic immune modulation. Here we show that sulforaphane (SFN), a compound derived from plants of the Brassicaceae family, e.g., broccoli, induces a pro-oxidative state in untransformed human T-cells of healthy donors or RA patients. This manifested as an increase of intracellular ROS and a marked decrease of GSH. Consistently, increased global cysteine sulfenylation was detected. Importantly, a major target for SFN-mediated protein oxidation was STAT3, a transcription factor involved in the regulation of TH17-related genes. Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and downregulated the expression of the transcription factor RORγt, and the TH17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases. The inhibitory effects of SFN could be abolished by exogenously supplied GSH and by the GSH replenishing antioxidant N-acetylcysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance SFN. It specifically exerts TH17 prone immunosuppressive effects on untransformed human T-cells by decreasing GSH and accumulation of ROS. Thus, SFN may offer novel clinical options for the treatment of TH17 related chronic inflammatory/autoimmune diseases such as rheumatoid arthritis.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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